title: Influence of normal mammary epithelium on breast cancer progression: the protective role of early pregnancy.
abstract: OBJECTIVE
  The microenvironment has a well recognized role in breast cancer progression. Despite different theories, the mechanism of early pregnancy protection in mammary carcinogenesis is unknown. Since pregnancy is responsible for mammary gland differentiation, we tested the hypothesis that differentiated mammary epithelial cells may inhibit breast cancer progression. In other words, the protective role of early pregnancy could be due to the inhibitory influences of the more differentiated mammary tissue.
  
  
  METHODS
  In order to test our hypothesis, we used 30 female Balb/c nude mice and MCF-7 cells of breast adenocarcinoma. The female mice were divided into two test groups, group I (GI) and group II (GII), and a control group. In GII, the animals were submitted to epithelial removal in the left fourth inguinal mammary gland at 3 weeks of age. Both groups were given continuous hormonal treatment to simulate the pregnancy development of the mammary gland. Two million MCF-7 cells were then injected into the fourth inguinal mammary gland (GI) or in the respective cleared mammary fat pad (GII). Five weeks later the mice were sacrificed and their tumors removed. Tumor development rates and tumor volumes were determined and proliferation and apoptosis were evaluated by immunohistochemistry.
  
  
  RESULTS
  Tumors of GII mice had a larger mean volume than those of GI mice (P = 0.001, Mann-Whitney U-test) and an apparent increase in proliferation, demonstrated by a higher staining intensity for proliferating cell nuclear antigen (PCNA). As tumors presented caspase 8 staining, there may be apoptotic activation involved in cell death, mainly through an extrinsic pathway.
  
  
  CONCLUSIONS
  These results suggest that a differentiated intact mammary gland may have an inhibitory influence on mammary tumor growth in mice.
authors.affiliation: Department of Gynecology ,University Hospital of Coimbra, Portugal. filipe_martins@dfci.harvard.edu
authors.forename: Filipe Correia
authors.initials: FC
authors.lastname: Martins
authors.forename: Maria Filomena
authors.initials: MF
authors.lastname: Botelho
authors.forename: António Manuel
authors.initials: AM
authors.lastname: Cabrita
authors.forename: Carlos Freire
authors.initials: CF
authors.lastname: de Oliveira
mesh_terms: D000367:Age Factors; D000818:Animals; D017209:Apoptosis; D001940:Breast / Q000254:growth & development* / Q000473:pathology; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D018450:Disease Progression; D004847:Epithelial Cells / Q000473:pathology*; D005260:Female; D007150:Immunohistochemistry; D008321:Mammary Glands, Animal / Q000254:growth & development / Q000473:pathology*; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011247:Pregnancy; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis
chemical_list: D018809:Proliferating Cell Nuclear Antigen